This invention relates to a novel polypeptide and a process for producing the same, more particularly to a novel polypeptide having an action of lowering Ca.sup.2+ concentration in blood and a process for producing the same.
Calcitonin (hereinafter called "CT") has hitherto been known as a polypeptide having the action of lowering Ca.sup.2+ concentration in blood. CT can be collected by extraction from thyroid glands of various mammals such as human being or from ultimobranchial glands of fish, cyclostomata, birds, its amino acid primary sequence has been clarified, and a number of synthetic CT's with similar structures based on this sequence have also been reported. These CT's derived from animals are all polypeptides consisting of 32 constituent amino acids, and all common in that the first and the seventh amino acids are L-cysteine, mercapto groups of both form a disulfide bonding and the carboxylic group end (hereinafter called "C-end") is prolineamide.
Recently, the present inventors extracted and purified CT from the ultimobranchial glands of chickens and determined its structure to find that it has a structure entirely different from those known in the art represented by the following formula (I): ##STR3## wherein Cys represents cysteine, Ala alanine, Ser serine, Leu leucine, Thr threonine, Val valine, Gly glycine, Lys lysine, Gln glutamine, Glu glutamic acid, His histidine, Tyr tyrosine, Pro proline, Arg arginine, Asp aspartic acid.
This CT has biological activity which is equal to or higher than CT's of cyclostomata and fish, and has already been published as Japanese Provisional Patent Publication No. 123500/1985 (which corresponds to U.S. Ser. No. 679,465 and European Patent Application No. 84 114 768.9).
The chicken CT is expected to be a novel pharmaceutical, useful for various symptoms such as Paget'disease, osteroporosis or hypercalcemia in which Ca.sup.2+ concentration in blood is abnormally high. However, for making this acceptable as a pharmaceutical, it is necessary to overcome the problem caused by the disulfide bonding possessed by the chicken CT, which is estimated to be very unstable in solutions and may cause a lowering of its physiological activity. Accordingly, the present inventors have made extensive studies, to obtain a stable CT derivative even in a solution state on the basis of the structure of the chicken CT, and consequently found that the above object can be accomplished by using in place of the first and the seventh cysteine in the chicken CT .alpha.-amino acid of the following formula (II): ##STR4## wherein n represents an integer of 3 to 7, and effecting ring closure between the side chain carboxylic group of said amino acid and the amino acid at the amino group end (hereinafter called "N-end"), namely the amino group of alanine, to accomplish the present invention.